It is well known that there are several different types of voltage-gated calcium channels which can be distinguished on the basis of biophysical and pharmacological properties. These calcium channels are defined by differences in the amino acid sequence of the .alpha..sub.1 subunits ("Molecular Determinants of Ca.sup.2+ Channel Function and Drug Action" TiPS 1995, 16, 43-49), and by different sensitivities to various ligands ("Synthetic Organic Ligands Active at Voltage-Gated Calcium Channels", Ann. N.Y. Acad. Sci., 1991, 635, 123-138). These publications teach that the L-type calcium channel differs from the N-type calcium channel in regard to the amino acid sequence of the .alpha..sub.1 subunits and the sensitivity to dihydropyridines (L-channels are sensitive, N-channels are not) and the sensitivity to .omega.-Conotoxins GVIA and MVIIA (N-channels are sensitive, L-channels are not).
L-Type calcium channel antagonists are clinically proven compounds for the treatment of cardiovascular disease, particularly hypertension.
The use of compounds which bind to N-type neuronal calcium channels has been discussed with respect to the treatment of a range of disorders involving abnormal calcium flux in cells, including ischaemia, Alzheimer's disease, neuroprotection and analgesia ("Neuronal Voltage-Sensitive Calcium Channels" Drug News & Perspectives, 1994, 7, 261-268). N-Type neuronal calcium channels have also been found to be involved in the release of various neurotransmitters and therefore, compounds that bind to N-type calcium channels may also be useful in various disease states characterized by abnormal neurotransmitter release, for example, anxiety, schizophrenia, Parkinson's disease and migraine.
Patent application EP 0 202 654 discloses 5-carboxy-1,4-dihydropyrimidine derivatives of general structure: ##STR2## as cardiovascular agents, particularly, by virtue of their vasodilator activity, as antihypertensive agents. These compounds are distinguished from the scope of the present application by virtue of the definition of the group R.sup.2 and by their different pharmacological activity.
Patent application JP 62-267272 discloses dihydropyrimidines of general structure: ##STR3## as agents for the treatment of circulation disorders. These compounds are distinguished from the scope of the present application by virtue of the definitions of groups R.sup.3 and R.sup.4, and by their different pharmacological activity.